ArticleThe Journal of biological chemistry2015
Heterotrimeric G proteins directly regulate MMP14/membrane type-1 matrix metalloprotease: a novel mechanism for GPCR-EGFR transactivation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Cathelicidin LL-37 promotes EMT, migration and metastasis of hepatocellular carcinoma cells in vitro and mouse model.Cell adhesion & migration · 2023Article
- Growth factors and their roles in cardiac development and regeneration: a narrative review.Pediatric medicine (Hong Kong, China) · 2023Article
- Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but Downregulated in Thick Tumours.Acta dermato-venereologica · 2023Article
- Neurokinin-1 receptor promotes non-small cell lung cancer progression through transactivation of EGFR.Cell death & disease · 2022Article
- Mu-opioid receptor and receptor tyrosine kinase crosstalk: Implications in mechanisms of opioid tolerance, reduced analgesia to neuropathic pain, dependence, and reward.Frontiers in systems neuroscience · 2022Review
- Transactivation of G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs): Recent insights using luminescence and fluorescence technologies.Current opinion in endocrine and metabolic research · 2021Review
- Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer.Disease markers · 2021Article
- A nongenomic mechanism for "metalloestrogenic" effects of cadmium in human uterine leiomyoma cells through G protein-coupled estrogen receptor.Archives of toxicology · 2019Article
- Neurotensin as a source of cyclic AMP and co-mitogen in fibrolamellar hepatocellular carcinoma.Oncotarget · 2019Article
- The Expanding Role of MT1-MMP in Cancer Progression.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Long non-coding RNA CCAT1 promotes cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis.Cell cycle (Georgetown, Tex.) · 2019Article
- The role of PAK1 in the sensitivity of kidney epithelial cells to ischemia-like conditions.Cell cycle (Georgetown, Tex.) · 2019Article
- Transactivation of RAGE mediates angiotensin-induced inflammation and atherogenesis.The Journal of clinical investigation · 2019Article
- Agonist-Biased Signaling via Matrix Metalloproteinase-9 Promotes Extracellular Matrix Remodeling.Cells · 2018Review
- Article
- G Protein Coupled Receptor-mediated Transactivation of Extracellular Proteases.Journal of cardiovascular pharmacology · 2017Review
- Cardiac GPCR-Mediated EGFR Transactivation: Impact and Therapeutic Implications.Journal of cardiovascular pharmacology · 2017Review
- Insights into cellular signalling by G protein coupled receptor transactivation of cell surface protein kinase receptors.Journal of cell communication and signaling · 2017Review
- Interacting post-muscarinic receptor signaling pathways potentiate matrix metalloproteinase-1 expression and invasion of human colon cancer cells.The Biochemical journal · 2017Article
- Membrane-anchored proteases in endothelial cell biology.Current opinion in hematology · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Agonist stimulation of G protein-coupled receptors (GPCRs) can transactivate epidermal growth factor receptors (EGFRs), but the precise mechanisms for this transactivation have not been defined. Key to this process is the protease-mediated "shedding" of membrane-tethered ligands, which then activate EGFRs. The specific proteases and the events involved in GPCR-EGFR transactivation are not fully understood. We have tested the hypothesis that transactivation can occur by a membrane-delimited process: direct increase in the activity of membrane type-1 matrix metalloprotease (MMP14, MT1-MMP) by heterotrimeric G proteins, and in turn, the generation of heparin-binding epidermal growth factor (HB-EGF) and activation of EGFR. Using membranes prepared from adult rat cardiac myocytes and fibroblasts, we found that MMP14 activity is increased by angiotensin II, phenylephrine, GTP, and guanosine 5'-O-[γ-thio]triphosphate (GTPγS). MMP14 activation by GTPγS occurs in a concentration- and time-dependent manner, does not occur in response to GMP or adenosine 5'-[γ-thio]triphosphate (ATPγS), and is not blunted by inhibitors of Src, PKC, phospholipase C (PLC), PI3K, or soluble MMPs. This activation is specific to MMP14 as it is inhibited by a specific MMP14 peptide inhibitor and siRNA knockdown. MMP14 activation by GTPγS is pertussis toxin-sensitive. A role for heterotrimeric G protein βγ subunits was shown by using the Gβγ inhibitor gallein and the direct activation of recombinant MMP14 by purified βγ subunits. GTPγS-stimulated activation of MMP14 also results in membrane release of HB-EGF and the activation of EGFR. These results define a previously unrecognized, membrane-delimited mechanism for EGFR transactivation via direct G protein activation of MMP14 and identify MMP14 as a heterotrimeric G protein-regulated effector.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.